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Neuroscience and Biobehavioral Reviews Aug 2015N-acetylcysteine (NAC) is recognized for its role in acetaminophen overdose and as a mucolytic. Over the past decade, there has been growing evidence for the use of NAC... (Review)
Review
N-acetylcysteine (NAC) is recognized for its role in acetaminophen overdose and as a mucolytic. Over the past decade, there has been growing evidence for the use of NAC in treating psychiatric and neurological disorders, considering its role in attenuating pathophysiological processes associated with these disorders, including oxidative stress, apoptosis, mitochondrial dysfunction, neuroinflammation and glutamate and dopamine dysregulation. In this systematic review we find favorable evidence for the use of NAC in several psychiatric and neurological disorders, particularly autism, Alzheimer's disease, cocaine and cannabis addiction, bipolar disorder, depression, trichotillomania, nail biting, skin picking, obsessive-compulsive disorder, schizophrenia, drug-induced neuropathy and progressive myoclonic epilepsy. Disorders such as anxiety, attention deficit hyperactivity disorder and mild traumatic brain injury have preliminary evidence and require larger confirmatory studies while current evidence does not support the use of NAC in gambling, methamphetamine and nicotine addictions and amyotrophic lateral sclerosis. Overall, NAC treatment appears to be safe and tolerable. Further well designed, larger controlled trials are needed for specific psychiatric and neurological disorders where the evidence is favorable.
Topics: Acetylcysteine; Adolescent; Adult; Clinical Trials as Topic; Female; Humans; Male; Mental Disorders; Nervous System Diseases; Neurology; Psychiatry; Randomized Controlled Trials as Topic; Treatment Outcome; Young Adult
PubMed: 25957927
DOI: 10.1016/j.neubiorev.2015.04.015 -
Przeglad Gastroenterologiczny 2022There are discordant reports on N-acetylcysteine (NAC) efficacy in non-acetaminophen acute liver failure (ALF). (Review)
Review
INTRODUCTION
There are discordant reports on N-acetylcysteine (NAC) efficacy in non-acetaminophen acute liver failure (ALF).
AIM
To determine whether NAC is beneficial in non-acetaminophen ALF.
MATERIAL AND METHODS
We performed a systemic review and meta-analysis of published data to address the question. PubMed and MEDLINE were searched using the terms non-acetylcysteine and ALF due to non-acetaminophen, viral infection, drug-induced or autoimmune hepatitis. The primary outcome was overall mortality. Secondary outcomes were transplant-free survival and length of hospital stay. Risk ratios were calculated using a random model for meta-analysis.
RESULTS
A total of 672 patients were included in this meta-analysis from 5 prospective studies (NAC group: = 334; control group: = 338). Viral hepatitis (45.8% vs. 32.8%) followed by drug-induced liver injury (24.6% vs. 27.5%), indeterminate cause (13.2% vs. 21.6%) and autoimmune hepatitis (6.6% vs. 8.9%) were the most common etiologies of ALF in the treatment group and control group respectively. Treatment with N-acetylcysteine improved the transplant-free survival significantly (55.1% vs. 28.1%; RR = 0.56; 95% CI: 0.33-0.94) whereas the overall survival was not improved with NAC (71% vs. 59.8%; RR = 0.73; 95% CI: 0.48-1.09). The NAC treatment was associated with shorter hospital stay (standard difference in means (SMD) = -1.62; 95% CI: -1.84 to -1.40, p < 0.001).
CONCLUSIONS
The treatment of patients with acute liver failure with N-acetylcysteine improved transplant-free survival and length of stay.
PubMed: 35371352
DOI: 10.5114/pg.2021.107797 -
Nutritional Neuroscience Jul 2023Individuals with bipolar disorder (BD) have higher rates of unhealthy lifestyles and risk for medical comorbidities Research currently suggests that dietary factors may...
INTRODUCTION
Individuals with bipolar disorder (BD) have higher rates of unhealthy lifestyles and risk for medical comorbidities Research currently suggests that dietary factors may play a role in the development of depression and anxiety. Therefore, nutritional approaches are potential strategies for the treatment of BD. The aim of this review is to summarize the available evidence on nutrition and BD.
MATERIALS AND METHODS
The paper was developed based on PRISMA 2020 guidelines. The search was conducted in Sep-2021 using PubMed and Cochrane Library, augmented by manually checked references lists. The search found 986 studies, of which 47 were included, combined with 13 from reference lists, totaling 60 studies.
RESULTS
There were 33 observational trials, of which 15 focused on fatty acids, 9 on micronutrients, 5 on specific foods, 4 on macro and micronutrients. The 27 interventional studies mainly focused on fatty acids, micronutrients and N-acetylcysteine (NAC).
DISCUSSION
Dietary intake or supplementation of unsaturated fatty acids, mainly Omega-3 seems to be associated with improved BD symptoms, along with seafood, folic acid and zinc. Studies found variable, mainly non-significant impacts of creatine, carnitine, vitamin D, inositol or NAC supplementation on BD. There are promising results associated with Coenzyme Q10 (Coq10) and probiotics. Taken together, these preliminary findings suggest that dietetic approaches might be included as part of BD treatment. Also considering the high risk of metabolic disorders in individuals with BD, they should be encouraged to choose healthy dietary lifestyles, including daily intake of fruits, vegetables, seafood and whole grains.
Topics: Humans; Bipolar Disorder; Diet; Vitamins; Micronutrients; Fatty Acids, Omega-3; Acetylcysteine
PubMed: 35608150
DOI: 10.1080/1028415X.2022.2077031 -
Annals of Internal Medicine Mar 2016N-acetylcysteine, sodium bicarbonate, statins, and ascorbic acid have been studied for reducing contrast-induced nephropathy (CIN). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
N-acetylcysteine, sodium bicarbonate, statins, and ascorbic acid have been studied for reducing contrast-induced nephropathy (CIN).
PURPOSE
To evaluate the comparative effectiveness of interventions to reduce CIN in adults receiving contrast media.
DATA SOURCES
MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, and Scopus databases through June 2015. Risk of bias and overall strength of evidence (SOE) of studies were assessed.
STUDY SELECTION
Randomized, controlled trials of N-acetylcysteine, sodium bicarbonate, statins, or ascorbic acid that used intravenous (IV) or intra-arterial contrast media and defined CIN with enough data for meta-analysis.
DATA EXTRACTION
Two reviewers independently extracted data and assessed study quality.
DATA SYNTHESIS
Low-dose N-acetylcysteine plus IV saline compared with IV saline (risk ratio [RR], 0.75 [95% CI, 0.63 to 0.89]; low SOE), N-acetylcysteine plus IV saline compared with IV saline in patients receiving low-osmolar contrast media (RR, 0.69 [CI, 0.58 to 0.84]; moderate SOE), and statins plus N-acetylcysteine plus IV saline versus N-acetylcysteine plus IV saline (RR, 0.52 [CI, 0.29 to 0.93]; low SOE) had clinically important and statistically significant benefits. The following 3 comparisons suggested a clinically important difference that was not statistically significant: sodium bicarbonate versus IV saline in patients receiving low-osmolar contrast media (RR, 0.65 [CI, 0.33 to 1.25]; low SOE), statins plus IV saline versus IV saline (RR, 0.68 [CI, 0.39 to 1.20]; low SOE), and ascorbic acid versus IV saline (RR, 0.72 [CI, 0.48 to 1.01]; low SOE). Strength of evidence was generally insufficient for comparisons of the need for renal replacement, cardiac events, and mortality.
LIMITATION
Too few studies were done in patients receiving IV contrast media.
CONCLUSION
The greatest reduction in CIN was seen with N-acetylcysteine plus IV saline in patients receiving LOCM and with statins plus N-acetylcysteine plus IV saline.
PRIMARY FUNDING SOURCE
Agency for Healthcare Research and Quality.
Topics: Acetylcysteine; Antioxidants; Ascorbic Acid; Contrast Media; Free Radical Scavengers; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Infusions, Intra-Arterial; Infusions, Intravenous; Kidney Diseases; Odds Ratio; Sodium Bicarbonate; Sodium Chloride; United States
PubMed: 26830221
DOI: 10.7326/M15-1456 -
The Cochrane Database of Systematic... Feb 2018Paracetamol (acetaminophen) is the most widely used non-prescription analgesic in the world. Paracetamol is commonly taken in overdose either deliberately or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Paracetamol (acetaminophen) is the most widely used non-prescription analgesic in the world. Paracetamol is commonly taken in overdose either deliberately or unintentionally. In high-income countries, paracetamol toxicity is a common cause of acute liver injury. There are various interventions to treat paracetamol poisoning, depending on the clinical status of the person. These interventions include inhibiting the absorption of paracetamol from the gastrointestinal tract (decontamination), removal of paracetamol from the vascular system, and antidotes to prevent the formation of, or to detoxify, metabolites.
OBJECTIVES
To assess the benefits and harms of interventions for paracetamol overdosage irrespective of the cause of the overdose.
SEARCH METHODS
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (January 2017), CENTRAL (2016, Issue 11), MEDLINE (1946 to January 2017), Embase (1974 to January 2017), and Science Citation Index Expanded (1900 to January 2017). We also searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov database (US National Institute of Health) for any ongoing or completed trials (January 2017). We examined the reference lists of relevant papers identified by the search and other published reviews.
SELECTION CRITERIA
Randomised clinical trials assessing benefits and harms of interventions in people who have ingested a paracetamol overdose. The interventions could have been gastric lavage, ipecacuanha, or activated charcoal, or various extracorporeal treatments, or antidotes. The interventions could have been compared with placebo, no intervention, or to each other in differing regimens.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data from the included trials. We used fixed-effect and random-effects Peto odds ratios (OR) with 95% confidence intervals (CI) for analysis of the review outcomes. We used the Cochrane 'Risk of bias' tool to assess the risks of bias (i.e. systematic errors leading to overestimation of benefits and underestimation of harms). We used Trial Sequential Analysis to control risks of random errors (i.e. play of chance) and GRADE to assess the quality of the evidence and constructed 'Summary of findings' tables using GRADE software.
MAIN RESULTS
We identified 11 randomised clinical trials (of which one acetylcysteine trial was abandoned due to low numbers recruited), assessing several different interventions in 700 participants. The variety of interventions studied included decontamination, extracorporeal measures, and antidotes to detoxify paracetamol's toxic metabolite; which included methionine, cysteamine, dimercaprol, or acetylcysteine. There were no randomised clinical trials of agents that inhibit cytochrome P-450 to decrease the activation of the toxic metabolite N-acetyl-p-benzoquinone imine.Of the 11 trials, only two had two common outcomes, and hence, we could only meta-analyse two comparisons. Each of the remaining comparisons included outcome data from one trial only and hence their results are presented as described in the trials. All trial analyses lack power to access efficacy. Furthermore, all the trials were at high risk of bias. Accordingly, the quality of evidence was low or very low for all comparisons. Interventions that prevent absorption, such as gastric lavage, ipecacuanha, or activated charcoal were compared with placebo or no intervention and with each other in one four-armed randomised clinical trial involving 60 participants with an uncertain randomisation procedure and hence very low quality. The trial presented results on lowering plasma paracetamol levels. Activated charcoal seemed to reduce the absorption of paracetamol, but the clinical benefits were unclear. Activated charcoal seemed to have the best risk:benefit ratio among gastric lavage, ipecacuanha, or supportive treatment if given within four hours of ingestion. There seemed to be no difference between gastric lavage and ipecacuanha, but gastric lavage and ipecacuanha seemed more effective than no treatment (very low quality of evidence). Extracorporeal interventions included charcoal haemoperfusion compared with conventional treatment (supportive care including gastric lavage, intravenous fluids, and fresh frozen plasma) in one trial with 16 participants. The mean cumulative amount of paracetamol removed was 1.4 g. One participant from the haemoperfusion group who had ingested 135 g of paracetamol, died. There were no deaths in the conventional treatment group. Accordingly, we found no benefit of charcoal haemoperfusion (very low quality of evidence). Acetylcysteine appeared superior to placebo and had fewer adverse effects when compared with dimercaprol or cysteamine. Acetylcysteine superiority to methionine was unproven. One small trial (low quality evidence) found that acetylcysteine may reduce mortality in people with fulminant hepatic failure (Peto OR 0.29, 95% CI 0.09 to 0.94). The most recent randomised clinical trials studied different acetylcysteine regimens, with the primary outcome being adverse events. It was unclear which acetylcysteine treatment protocol offered the best efficacy, as most trials were underpowered to look at this outcome. One trial showed that a modified 12-hour acetylcysteine regimen with a two-hour acetylcysteine 100 mg/kg bodyweight loading dose was associated with significantly fewer adverse reactions compared with the traditional three-bag 20.25-hour regimen (low quality of evidence). All Trial Sequential Analyses showed lack of sufficient power. Children were not included in the majority of trials. Hence, the evidence pertains only to adults.
AUTHORS' CONCLUSIONS
These results highlight the paucity of randomised clinical trials comparing different interventions for paracetamol overdose and their routes of administration and the low or very low level quality of the evidence that is available. Evidence from a single trial found activated charcoal seemed the best choice to reduce absorption of paracetamol. Acetylcysteine should be given to people at risk of toxicity including people presenting with liver failure. Further randomised clinical trials with low risk of bias and adequate number of participants are required to determine which regimen results in the fewest adverse effects with the best efficacy. Current management of paracetamol poisoning worldwide involves the administration of intravenous or oral acetylcysteine which is based mainly on observational studies. Results from these observational studies indicate that treatment with acetylcysteine seems to result in a decrease in morbidity and mortality, However, further evidence from randomised clinical trials comparing different treatments are needed.
Topics: Acetaminophen; Acetylcysteine; Analgesics, Non-Narcotic; Antidotes; Charcoal; Cysteamine; Dimercaprol; Drug Overdose; Gastric Lavage; Humans; Intestinal Absorption; Liver Failure, Acute; Liver Transplantation; Methionine; Randomized Controlled Trials as Topic
PubMed: 29473717
DOI: 10.1002/14651858.CD003328.pub3 -
Medical treatments for idiopathic pulmonary fibrosis: a systematic review and network meta-analysis.Thorax Dec 2022Idiopathic pulmonary fibrosis (IPF) is a respiratory disorder with a poor prognosis. Our objective is to assess the comparative effectiveness of 22 approved or studied... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is a respiratory disorder with a poor prognosis. Our objective is to assess the comparative effectiveness of 22 approved or studied IPF drug treatments.
METHODS
We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov from inception to 2 April 2021. We included randomised controlled trials (RCTs) for adult patients with IPF receiving one or more of 22 drug treatments. Pairs of reviewers independently identified randomised trials that compared one or more of the target medical treatments in patients with IPF. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for network meta-analysis. We calculated pooled relative risk (RR) ratios and presented direct or network estimates with 95% credibility intervals (95% CI), within the GRADE framework.
RESULTS
We identified 48 (10 326 patients) eligible studies for analysis. Nintedanib [RR 0.69 (0.44 to 1.1), pirfenidone [RR 0.63 (0.37 to 1.09); direct estimate), and sildenafil [RR (0.44 (0.16 to 1.09)] probably reduce mortality (all moderate certainty). Nintedanib (2.92% (1.51 to 4.14)), nintedanib+sildenafil (157 mL (-88.35 to 411.12)), pirfenidone (2.47% (-0.1 to 5)), pamrevlumab (4.3% (0.5 to 8.1)) and pentraxin (2.74% (1 to 4.83)) probably reduce decline of overall forced vital capacity (all moderate certainty). Only sildenafil probably reduces acute exacerbation and hospitalisations (moderate certainty). Corticosteroids+azathioprine+N-acetylcysteine increased risk of serious adverse events versus placebo (high certainty).
CONCLUSION AND RELEVANCE
Future guidelines should consider sildenafil for IPF and further research needs to be done on promising IPF treatments such as pamrevlumab and pentraxin as phase 3 trials are completed.
Topics: Adult; Humans; Idiopathic Pulmonary Fibrosis; Network Meta-Analysis; Sildenafil Citrate; Azathioprine; Acetylcysteine
PubMed: 35145039
DOI: 10.1136/thoraxjnl-2021-217976 -
The Cochrane Database of Systematic... Aug 2022Urinary tract infections (UTIs) are very common, affecting more than 7 million people worldwide. Whilst many people may only experience a single episode in their... (Review)
Review
BACKGROUND
Urinary tract infections (UTIs) are very common, affecting more than 7 million people worldwide. Whilst many people may only experience a single episode in their lifetime and are generally responsive to standard antibiotics, a significant proportion of adults and children (approximately 15% to 25%) are chronic symptomatic UTI sufferers. Certain population groups are at greater risk than others, such as immunosuppressed and people with chronic kidney disease. D-mannose is a sugar part of normal human metabolism found within most diets. The mechanism of action is to prevent bacterial adherence to the uroepithelial cells. The D-mannose-based inhibitors can block uropathogenic Escherichia coli adhesion and invasion of the uroepithelial cells. The bacteria are then understood to essentially be eliminated by urination. Early pilot studies on animals and humans have trialled concentrated forms of D-mannose (tablets or sachets) in doses ranging from 200 mg up to 2 to 3 g and found possible efficacy in reducing UTI symptoms or recurrence. Although the anti-adhesive effects of D-mannose have been well-established, only recently have we seen a small number of pilot studies and small clinical trials conducted.
OBJECTIVES
To assess the benefits and harms of D-mannose for preventing and treating UTIs in adults and children.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 22 February 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
We included RCTs measuring and reporting the effect of D-mannose, in any combination and any formulation, to prevent or treat UTIs in adults and children, females and males, in any setting (including perioperative). Authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria.
DATA COLLECTION AND ANALYSIS
Data extraction was independently carried out by two authors using a standard data extraction form. Methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another author. The certainty of the evidence was assessed using the GRADE approach.
MAIN RESULTS
We included seven RCTs (719 participants) in adult females and males who had either acute cystitis or a history of recurrent (at least two episodes in six months or three episodes in 12 months) UTIs (symptomatic or asymptomatic). Two were prevention studies, four were prevention and treatment studies (two perioperative and one in people with multiple sclerosis), and one was a treatment study. Time periods ranged from 15 days to six months. No two studies were comparable (by dose or treatments), and we could not undertake meta-analyses. Individual studies reported no clear evidence to determine whether D-mannose is more or less effective in preventing or treating UTIs. D-mannose (2 g) had uncertain effects on symptomatic and bacteriuria-confirmed UTIs when compared to no treatment (1 study, 205 participants; very low certainty evidence) and antibiotics (nitrofurantoin 50 mg) (1 study, 206 participants; very low certainty evidence). D-mannose, in combination with herbal supplements, had uncertain effects on symptomatic and bacteria-confirmed UTI and pain when compared to no treatment (1 study, 40 participants; very low certainty evidence). D-mannose 500 mg plus supplements (N-acetylcysteine and Morinda citrifolia fruit extract) had uncertain effects on symptomatic and bacteriuria-confirmed UTIs when compared to an antibiotic (prulifloxacin 400 mg) (1 study, 75 participants; very low certainty evidence). Adverse events were very few and poorly reported; none were serious (mostly diarrhoea and vaginal burning). Overall, the quality of the evidence is poor. Most studies were judged to have unclear or high risk of bias across most domains. Data was sparse and addressed very few outcomes. The GRADE evaluation was rated as very low certainty evidence due to very serious limitations in the study design or execution (high risk of bias across all studies) and sparse data (single study data and small sample sizes).
AUTHORS' CONCLUSIONS
There is currently little to no evidence to support or refute the use of D-mannose to prevent or treat UTIs in all populations. This review highlights the severe lack of high-quality RCTs testing the efficacy of D-mannose for UTIs in any population. Despite UTIs being one of the most common adult infections (affecting 50% of women at least once in their lifetime) and the growing global antimicrobial resistance, we found very few studies that adequately test this alternative treatment. Future research in this field requires, in the first instance, a single adequately powered RCT comparing D-mannose with placebo.
Topics: Adult; Anti-Bacterial Agents; Bacteriuria; Child; Female; Humans; Kidney; Male; Mannose; Urinary Tract Infections
PubMed: 36041061
DOI: 10.1002/14651858.CD013608.pub2 -
The Cochrane Database of Systematic... Mar 2022Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome are rare, severe cutaneous adverse reactions usually triggered by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome are rare, severe cutaneous adverse reactions usually triggered by medications. In addition to tertiary-level supportive care, various systemic therapies have been used including glucocorticoids, intravenous immunoglobulins (IVIGs), cyclosporin, N-acetylcysteine, thalidomide, infliximab, etanercept, and plasmapheresis. There is an unmet need to understand the efficacy of these interventions.
OBJECTIVES
To assess the effects of systemic therapies (medicines delivered orally, intramuscularly, or intravenously) for the treatment of SJS, TEN, and SJS/TEN overlap syndrome.
SEARCH METHODS
We searched the following databases up to March 2021: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We also searched five clinical trial registers, the reference lists of all included studies and of key review articles, and a number of drug manufacturer websites. We searched for errata or retractions of included studies.
SELECTION CRITERIA
We included only randomised controlled trials (RCTs) and prospective observational comparative studies of participants of any age with a clinical diagnosis of SJS, TEN, or SJS/TEN overlap syndrome. We included all systemic therapies studied to date and permitted comparisons between each therapy, as well as between therapy and placebo.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as specified by Cochrane. Our primary outcomes were SJS/TEN-specific mortality and adverse effects leading to discontinuation of SJS/TEN therapy. Secondary outcomes included time to complete re-epithelialisation, intensive care unit length of stay, total hospital length of stay, illness sequelae, and other adverse effects attributed to systemic therapy. We rated the certainty of the evidence for each outcome using GRADE.
MAIN RESULTS
We included nine studies with a total of 308 participants (131 males and 155 females) from seven countries. We included two studies in the quantitative meta-analysis. We included three RCTs and six prospective, controlled observational studies. Sample sizes ranged from 10 to 91. Most studies did not report study duration or time to follow-up. Two studies reported a mean SCORe of Toxic Epidermal Necrosis (SCORTEN) of 3 and 1.9. Seven studies did not report SCORTEN, although four of these studies reported average or ranges of body surface area (BSA) (means ranging from 44% to 51%). Two studies were set in burns units, two in dermatology wards, one in an intensive care unit, one in a paediatric ward, and three in unspecified inpatient units. Seven studies reported a mean age, which ranged from 29 to 56 years. Two studies included paediatric participants (23 children). We assessed the results from one of three RCTs as low risk of bias in all domains, one as high, and one as some concerns. We judged the results from all six prospective observational comparative studies to be at a high risk of bias. We downgraded the certainty of the evidence because of serious risk of bias concerns and for imprecision due to small numbers of participants. The interventions assessed included systemic corticosteroids, tumour necrosis factor-alpha (TNF-alpha) inhibitors, cyclosporin, thalidomide, N-acetylcysteine, IVIG, and supportive care. No data were available for the main comparisons of interest as specified in the review protocol: etanercept versus cyclosporin, etanercept versus IVIG, IVIG versus supportive care, IVIG versus cyclosporin, and cyclosporin versus corticosteroids. Corticosteroids versus no corticosteroids It is uncertain if there is any difference between corticosteroids (methylprednisolone 4 mg/kg/day for two more days after fever had subsided and no new lesions had developed) and no corticosteroids on disease-specific mortality (risk ratio (RR) 2.55, 95% confidence interval (CI) 0.72 to 9.03; 2 studies; 56 participants; very low-certainty evidence). Time to complete re-epithelialisation, length of hospital stay, and adverse effects leading to discontinuation of therapy were not reported. IVIG versus no IVIG It is uncertain if there is any difference between IVIG (0.2 to 0.5 g/kg cumulative dose over three days) and no IVIG in risk of disease-specific mortality (RR 0.33, 95% CI 0.04 to 2.91); time to complete re-epithelialisation (mean difference (MD) -2.93 days, 95% CI -4.4 to -1.46); or length of hospital stay (MD -2.00 days, 95% CI -5.81 to 1.81). All results in this comparison were based on one study with 36 participants, and very low-certainty evidence. Adverse effects leading to discontinuation of therapy were not reported. Etanercept (TNF-alpha inhibitor) versus corticosteroids Etanercept (25 mg (50 mg if weight > 65 kg) twice weekly "until skin lesions healed") may reduce disease-specific mortality compared to corticosteroids (intravenous prednisolone 1 to 1.5 mg/kg/day "until skin lesions healed") (RR 0.51, 95% CI 0.16 to 1.63; 1 study; 91 participants; low-certainty evidence); however, the CIs were consistent with possible benefit and possible harm. Serious adverse events, such as sepsis and respiratory failure, were reported in 5 of 48 participants with etanercept and 9 of 43 participants with corticosteroids, but it was not clear if they led to discontinuation of therapy. Time to complete re-epithelialisation and length of hospital stay were not reported. Cyclosporin versus IVIG It is uncertain if there is any difference between cyclosporin (3 mg/kg/day or intravenous 1 mg/kg/day until complete re-epithelialisation, then tapered off (10 mg/day reduction every 48 hours)) and IVIG (continuous infusion 0.75 g/kg/day for 4 days (total dose 3 g/kg) in participants with normal renal function) in risk of disease-specific mortality (RR 0.13, 95% CI 0.02 to 0.98, 1 study; 22 participants; very low-certainty evidence). Time to complete re-epithelialisation, length of hospital stay, and adverse effects leading to discontinuation of therapy were not reported. No studies measured intensive care unit length of stay.
AUTHORS' CONCLUSIONS
When compared to corticosteroids, etanercept may result in mortality reduction. For the following comparisons, the certainty of the evidence for disease-specific mortality is very low: corticosteroids versus no corticosteroids, IVIG versus no IVIG and cyclosporin versus IVIG. There is a need for more multicentric studies, focused on the most important clinical comparisons, to provide reliable answers about the best treatments for SJS/TEN.
Topics: Acetylcysteine; Adrenal Cortex Hormones; Adult; Autoimmune Diseases; Child; Cyclosporine; Etanercept; Female; Humans; Immunoglobulins, Intravenous; Male; Middle Aged; Observational Studies as Topic; Stevens-Johnson Syndrome; Thalidomide; Tumor Necrosis Factor-alpha
PubMed: 35274741
DOI: 10.1002/14651858.CD013130.pub2 -
The Journal of Clinical Psychiatry Apr 2016To assess the utility of N-acetylcysteine administration for depressive symptoms in subjects with psychiatric conditions using a systematic review and meta-analysis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the utility of N-acetylcysteine administration for depressive symptoms in subjects with psychiatric conditions using a systematic review and meta-analysis.
DATA SOURCES
A computerized literature search was conducted in MEDLINE, Embase, the Cochrane Library, SciELO, PsycINFO, Scopus, and Web of Knowledge. No year or country restrictions were used. The Boolean terms used for the electronic database search were (NAC OR N-acetylcysteine OR acetylcysteine) AND (depression OR depressive OR depressed) AND (trial). The last search was performed in November 2014.
STUDY SELECTION
The literature was searched for double-blind, randomized, placebo-controlled trials using N-acetylcysteine for depressive symptoms regardless of the main psychiatric condition. Using keywords and cross-referenced bibliographies, 38 studies were identified and examined in depth. Of those, 33 articles were rejected because inclusion criteria were not met. Finally, 5 studies were included.
DATA EXTRACTION
Data were extracted independently by 2 investigators. The primary outcome measure was change in depressive symptoms. Functionality, quality of life, and manic and anxiety symptoms were also examined. A full review and meta-analysis were performed. Standardized mean differences (SMDs) and odds ratios (ORs) with 95% CIs were calculated.
RESULTS
Five studies fulfilled our inclusion criteria for the meta-analysis, providing data on 574 participants, of whom 291 were randomized to receive N-acetylcysteine and 283 to placebo. The follow-up varied from 12 to 24 weeks. Two studies included subjects with bipolar disorder and current depressive symptoms, 1 included subjects with MDD in a current depressive episode, and 2 included subjects with depressive symptoms in the context of other psychiatric conditions (1 trichotillomania and 1 heavy smoking). Treatment with N-acetylcysteine improved depressive symptoms as assessed by Montgomery-Asberg Depression Rating Scale and Hamilton Depression Rating Scale when compared to placebo (SMD = 0.37; 95% CI = 0.19 to 0.55; P < .001). Subjects receiving N-acetylcysteine had better depressive symptoms scores on the Clinical Global Impressions-Severity of Illness scale at follow-up than subjects on placebo (SMD = 0.22; 95% CI = 0.03 to 0.41; P < .001). In addition, global functionality was better in N-acetylcysteine than in placebo conditions. There were no changes in quality of life. With regard to adverse events, only minor adverse events were associated with N-acetylcysteine (OR = 1.61; 95% CI = 1.01 to 2.59; P = .049).
CONCLUSIONS
Administration of N-acetylcysteine ameliorates depressive symptoms, improves functionality, and shows good tolerability.
Topics: Acetylcysteine; Activities of Daily Living; Depressive Disorder; Follow-Up Studies; Humans; Randomized Controlled Trials as Topic
PubMed: 27137430
DOI: 10.4088/JCP.15r09984 -
Biomedical Reports Aug 2022Several studies, reviews and meta-analyses have documented that D-mannose use lowers the risk of recurrent urinary tract infections (UTI), but its role in the treatment... (Review)
Review
Several studies, reviews and meta-analyses have documented that D-mannose use lowers the risk of recurrent urinary tract infections (UTI), but its role in the treatment of UTI/cystitis-related symptoms is unclear. In particular, no systematic review has analyzed the role of treatment with D-mannose in acute UTI/cystitis. In this paper, we systematically reviewed the published data on the effect of D-mannose, alone or in association with other compounds, on the typical symptoms of UTI/cystitis. PubMed/Medline and EMBASE databases were searched, from 1990 to January 2022, using combinations of the following keywords: 'urinary tract infections', 'cystalgia', 'recurrent next urinary tract infection', 'cystitis', 'mannose', 'mannoside', 'D-mannose', 'bacteriuria', 'pyuria', 'pyelocystitis' with the appropriate Boolean modifiers (Limits: Human, English, full article). Studies were selected for the systematic review if they were clinical studies and reported original data, the number of patients using D-mannose alone or in association with other treatments, and the number of patients with symptoms of UTI/cystitis at trial entry and after the follow-up period. A total of seven studies were identified. D-mannose was given alone in two studies, and was associated with cranberry extract, fruit extract, pomegranate extract, fructo-oligosaccharides, lactobacilli, and N-acetylcysteine in the others. All studies reported that symptoms decreased after treatment with D-mannose. Despite the limitations of the studies, the consistent results observed among all studies give support to the general findings that D-mannose may be useful in the treatment of UTI/cystitis symptoms.
PubMed: 35815191
DOI: 10.3892/br.2022.1552